{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:46:12Z","timestamp":1791276372413,"version":"4.1.0"},"reference-count":54,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2007,3,12]],"date-time":"2007-03-12T00:00:00Z","timestamp":1173657600000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2007,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background\/aims<\/jats:title><jats:p>Fibrosis occurs in most chronic liver injuries and results from changes in the balance between synthesis and degradation of extracellular matrix (ECM) components. Matrix metalloproteinases (MMPs) and their endogenous inhibitors (TIMPs) are known to regulate the ECM turnover. We investigate the effect of modified synthetic small interfering RNA (siRNA) targeting TIMP\u20102 in rat model of liver fibrosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Rat hepatic fibrosis was induced by CCl<jats:sub>4<\/jats:sub> for 8 weeks. After the 2\u2010week CCl<jats:sub>4<\/jats:sub> injection period, rats in the three siRNA groups simultaneously received a different dosage (0.05, 0.1 and 0.2 mg\u00b7kg<jats:sup>\u22121<\/jats:sup>, respectively) of modified synthetic siRNA targeting TIMP\u20102 via the tail vein every 3 days for 6 weeks. The pathological changes in liver tissues were observed by light microscopy and transmission electron microscopy. Portal vein pressure and proliferating cell nuclear antigen were measured. Expression of TIMP\u20102, MMP\u20102, MT1\u2010MMP, MMP\u201013, hepatocyte growth factor, collagen type I, collagen type III and \u03b1\u2010SMA were evaluated by quantitative real\u2010time polymerase chain reaction or Western blotting or gelatin zymography.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Modified synthetic siRNA targeting TIMP\u20102 induced a dose\u2010dependent inhibition of the TIMP\u20102 expression in the rat model of liver fibrosis with a similar trend in MMP\u20102 and MT1\u2010MMP, but an increase in MMP\u201013. Rats administered siRNA targeting TIMP\u20102 showed promotion of ECM degradation, reduction in activated hepatic stellate cells and enhancement of hepatocyte regeneration. Furthermore, portal hypertension was also ameliorated after treatment with siRNA targeting TIMP\u20102.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Knock\u2010down of TIMP\u20102 expression attenuates CCl<jats:sub>4<\/jats:sub>\u2010induced liver fibrosis and is a potential pharmacological target for gene therapy in liver fibrosis. 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